TP53 mutations was reported to be correlated to the efficacy of program death-1(PD-1)and program death ligand-1(PD-L1).The role of co-mutations of TP53 with other recurrently mutated genes in outcome of anti-PD-(L)1 t...TP53 mutations was reported to be correlated to the efficacy of program death-1(PD-1)and program death ligand-1(PD-L1).The role of co-mutations of TP53 with other recurrently mutated genes in outcome of anti-PD-(L)1 treatment for non-small cell lung cancer(NSCLC)is unknown.Here we mined a previously generated dataset to address the effect of co-mutations on the progression free survival(PFS)of NSCLC patients.Non-synonymous mutations and clinical data of 240 NSCLC patients with anti-PD-(L)1 based therapy was downloaded from cBioPortal.Totally 206 patients received monotherapy and 34 patients received combination therapy.In 240 NSCLC patients,TP53 mutation rate was 59.2%.For the monotherapy cohort,TP53 mutated NSCLC patients have a significantly longer PFS(4.3 vs.2.5 months,P=0.0019)compared with TP53 wild type NSCLC patients.The same tendency was also observed in the combination therapy cohort,but the difference in PFS(6.3 vs.5.4 months,P=0.12)was not significant.Ever-smoker had a longer PFS compared to never-smokers(4.0 vs.2.7 months).For further co-mutation analysis with TP53 including KEAP1 mutation(53/240,22.1%),KMT3C mutation(26/240,10.8%),STK11 mutation(56/240,23.3%),EGFR mutation(28/240,11.7%)and KRAS mutation(86/240,35.8%).Patients with both TP53 plus KEAP1 mutations in all 240 patients had a longer PFS compared with co-wild population(PFS 9.2 vs.4.2 months,P=0.012)when treated with PD-1/PD-L1 inhibitors.TP53 might be the dominating mutation correlating with longer PFS in PD-1/PD-L1 monotherapy.Different genes displayed distinct effect when co-mutated with TP53 in NSCLC patients.展开更多
基金This work was supported by Chinese Academy of Medical Sciences(No.2019XK320068).
文摘TP53 mutations was reported to be correlated to the efficacy of program death-1(PD-1)and program death ligand-1(PD-L1).The role of co-mutations of TP53 with other recurrently mutated genes in outcome of anti-PD-(L)1 treatment for non-small cell lung cancer(NSCLC)is unknown.Here we mined a previously generated dataset to address the effect of co-mutations on the progression free survival(PFS)of NSCLC patients.Non-synonymous mutations and clinical data of 240 NSCLC patients with anti-PD-(L)1 based therapy was downloaded from cBioPortal.Totally 206 patients received monotherapy and 34 patients received combination therapy.In 240 NSCLC patients,TP53 mutation rate was 59.2%.For the monotherapy cohort,TP53 mutated NSCLC patients have a significantly longer PFS(4.3 vs.2.5 months,P=0.0019)compared with TP53 wild type NSCLC patients.The same tendency was also observed in the combination therapy cohort,but the difference in PFS(6.3 vs.5.4 months,P=0.12)was not significant.Ever-smoker had a longer PFS compared to never-smokers(4.0 vs.2.7 months).For further co-mutation analysis with TP53 including KEAP1 mutation(53/240,22.1%),KMT3C mutation(26/240,10.8%),STK11 mutation(56/240,23.3%),EGFR mutation(28/240,11.7%)and KRAS mutation(86/240,35.8%).Patients with both TP53 plus KEAP1 mutations in all 240 patients had a longer PFS compared with co-wild population(PFS 9.2 vs.4.2 months,P=0.012)when treated with PD-1/PD-L1 inhibitors.TP53 might be the dominating mutation correlating with longer PFS in PD-1/PD-L1 monotherapy.Different genes displayed distinct effect when co-mutated with TP53 in NSCLC patients.
